Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1994-07-29
1997-07-15
Gerstl, Robert
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C07C40500
Patent
active
056485263
DESCRIPTION:
BRIEF SUMMARY
FIELD OF ART
The present invention relates to a process for preparing E-prostaglandins through the deallylation reaction of allyl esters of E-prostaglandins.
BACKGROUND ART
For the preparation of E-prostaglandins, a method is commonly used in which E-prostaglandins are extracted from the lower alkyl esters of E-prostaglandins. However, since E-prostaglandins are chemically labile and subject to dehydration reaction as they have .beta.-hydroxy-ketone in the skeleton, it is hardly possible to apply the ordinary chemical techniques for their preparation. Hydrolysis by use of an enzyme is known as a most effective method for the preparation of E-prostaglandins (JP-A-52-21392 and A. Hazato et al: Hydrolysis of E-Prostaglandin Methyl Esters Using Esterase, Bul. of Japan Chemical Society, Vol. 9, pp. 1390-1392, 1983).
However, this hydrolytic method using an enzyme has the disadvantage in that a great deal of time is required for the reaction in the case of certain types of E-prostaglandins. Further, in the preparation of E-prostaglandins having the triple bonds at the 13- and 14-positions (the compounds of the formula (II) in which B is ethynylene group), which are among prostaglandings E.sub.1, there would be produced the isomers of the objective compound, such as 8-.beta. compounds.
DISCLOSURE OF THE INVENTION
As a result of intensive studies for solving said problems, the present inventors found that when the allyl esters of E-prostaglandins are subjected to a deallylation reaction using a zero- or divalent palladium complex or its salt as catalyst, it is possible to produce the objective E-prostaglandins in a high yield and in a short time with minimized formation of isomers. The present invention has been attained on the basis of this finding.
The present invention provides a process for preparing E-prostaglandins represented by the following formula: ##STR3## (wherein A, R.sup.6 and R.sup.7 are each an arbitrary group which does not participate in the reaction; B is a vinylene or ethynylene group; and R.sup.4 and R.sup.5 may be the same or different from each other and each represents a hydrogen atom or a protective group of the hydroxyl group) which comprises reacting the allyl esters of E-prostaglandins represented by the following formula: ##STR4## (wherein R.sup.1 and R.sup.2 may be the same or different from each other and each represents a hydrogen atom or a lower alkyl group; R.sup.3 represents a hydrogen atom, a lower alkyl group, an alkenyl group or an aryl group; and A, B, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are as defined above) with at least one substance selected from the group consisting of bases and formic acid in the presence of a zero- or divalent palladium complex or its salt.
In the present invention, the typical examples of the groups represented by the formula --CH.sub.2 --CR.sup.1 .dbd.CR.sup.2 R.sup.3 (wherein R.sup.1, R.sup.2 and R.sup.3 represent the same as defined above) include those of the following formulae: ##STR5##
The protective group of the hydroxyl group may be any of those commonly used in the preparation of prostaglandins. Examples of such protective groups include t-butyldimethylsilyl group, triethylsilyl group, phenyldimethylsilyl group, t-butyldiphenylsilyl group, tetrahydropyranyl group, tetrahydrofuranyl group, methoxymethyl group, ethoxyethyl group and benzyl group.
A, R.sup.6 and R.sup.7 may each be any suitable group which does not participate in the reaction in the process of the present invention. For example, A may be a straight-chain C.sub.3-8 alkylene group (such as trimethylene group, tetramethylene group, hexamethylene group, octamethylene group, etc.), a straight-chain C.sub.3-9 alkenylene group [such as the groups represented by the following formulae: ##STR6## (wherein n.sub.1 is an integer of 1 to 6; n.sub.2 is an integer of 2 to 5; and n.sub.3 is an integer of 1 to 6)], a straight-chain C.sub.2-8 alkylene group having one oxygen or sulfur atom as intermediary in the molecular chain [such as the groups represented by the following formulae: a
REFERENCES:
The Chemical Society of Japan, No. 9 (1983) pp. 1390-1392.
Chemistry Letters, No. 10, Oct. 1992 pp. 2095-2098.
Kunz, Angew Chem. Int. Ed. Eng. 73 (1) 71 1984.
Amano Takehiro
Goto Jun
Kameo Kazuya
Mutoh Masaru
Ono Naoya
Gerstl Robert
Sato Fumie
Taisho Pharmaceutical Co. Ltd.
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